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dc.contributor.advisor Lingor, Paul Prof. Dr.
dc.contributor.author Carboni, Eleonora
dc.date.accessioned 2017-09-06T10:43:13Z
dc.date.available 2017-09-06T10:43:13Z
dc.date.issued 2017-09-06
dc.identifier.uri http://hdl.handle.net/11858/00-1735-0000-0023-3EF2-D
dc.language.iso eng de
dc.relation.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc 570 de
dc.title Alpha-synuclein aggregation: visualization by X-ray techniques and its modulation by iron de
dc.type doctoralThesis de
dc.contributor.referee Salditt, Tim Prof. Dr.
dc.date.examination 2016-10-19
dc.description.abstracteng Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. It’s a progressive disease that can be treated only symptomatically and its causes are still not fully understood. Two main factors have shown to play a pivotal role in the etiopathology of PD: the metal dys-homeostasis and the presence of aggregated protein structures (Lewy Bodies) that are mainly composed of the protein alpha-synuclein (aSyn). The present work had the aim of better characterizing the role of the interaction between aSyn and iron (Fe) in PD. A combination of X-ray-based imaging techniques together with cell-biology methods and animal models was applied for studying this interactions. The analysis showed for the first time the presence of mostly extracellularly located highly ordered structures in brain tissue of PD patients using x-ray diffraction techniques. The distribution and quantification of the trace metals in the samples exhibited an increased Fe content in line with previous data on metal dys-homeostasis in PD. Particle-induced X-ray emission was able to prove that aSyn overexpression affects the metal content in primary midbrain neurons in presence and in absence of excessive Fe supply. Furthermore, overexpression of aSyn changed the expression of metal transport proteins. A murine model of aSyn aggregation (prnp.aSyn.A53T) in combination with mild Fe intoxication showed that this interaction leaded to the appearance of motor learning deficits. In this murine paradigm DFP, a Fe chelator that is able to cross the blood brain barrier, could rescue the deleterious effects of Fe intoxication. This suggested that Fe chelators could be combined with the symptomatic therapies for PD for future treatments as first clinical trials with this drug also indicate. This work used a combination of biological and X-ray imaging techniques to shed a light on the interaction of aSyn and Fe and thus contributed to a deeper understanding of PD pathomechanisms and future disease-modifying translational therapies. de
dc.contributor.coReferee Outeiro, Tiago Fleming Prof. Dr.
dc.subject.eng iron de
dc.subject.eng X-ray de
dc.subject.eng X-ray diffraction de
dc.subject.eng X-ray fluorescence de
dc.subject.eng alpha-synuclein de
dc.subject.eng XRD de
dc.subject.eng XRF de
dc.subject.eng synuclein de
dc.subject.eng deferiprone de
dc.subject.eng mouse model de
dc.subject.eng behavioral test de
dc.subject.eng aggregation de
dc.subject.eng Parkinson's disease de
dc.subject.eng prnp.aSyn.A53T de
dc.subject.eng A53T de
dc.identifier.urn urn:nbn:de:gbv:7-11858/00-1735-0000-0023-3EF2-D-5
dc.affiliation.institute Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) de
dc.subject.gokfull Biologie (PPN619462639) de
dc.identifier.ppn 1006090991 1000140059

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